Bendamustine + Rituximab (BR) Project

Transcription

1 Bendamustine + Rituximab (BR) Project

2 Efficacy and tolerability of Bendamustine and Rituximab in first line and second line treatment in CLL An observational study proposed by the ERIC-GIMEMA groups Rationale for the study (first line) Bendamustine + Rituximab is the most widely employed regimen in first line in the young and in the elderly patient 1 In the published guidelines for the appropriate use of bendamustine in first-line therapy of CLL prepared on behalf of SIE, SIES, GITMO Group 2 the following unmet need were recognized: - efficacy and safety of BR in elderly patients - efficacy and safety of BR in unfit patients - efficacy of BR in different risk categories. 1 Green MR, ASH, 2014 abs # 4676 Cuneo A, et al Leuk Res, 2014

3 Subgroup analysis - Age 65 years; years and >75 years comorbidity 2 or more comorbidities - CIRS score 6 vs > 6 - Calculated creatinine clearance 70 vs > 70 ml/min (Cockcroft-Gault formula) - Bulky ( 5cm) lymphadenopathy vs patients without bulky lymph nodes - Advanced clinical stages (Rai III/IV, Binet C) vs other - FISH categories (17p-, 11q-, +12, 13q-) - IGHV mutational status (mutated vs unmutated) - CD38 (positive vs negative) - Analysis of the impact of TP53 mutation possible (amendment) - Other biologic markers can studied provided that their detection (e.g. CD49d, ZAP70) can be considered clinical practice

4 Efficacy and tolerability of Bendamustine and Rituximab in first line and second line treatment in CLL Data gap An observational study proposed by the ERIC-GIMEMA groups Rationale for the study (second line) - efficacy of chemoimmunotherapy in second line - efficacy of second line treatment in low-risk and high-risk patients Pharmacoeconomic considerations - Availability of new drugs is limited in a number of countries - Biosimilar rituximab soon available

5 TITLE: An observational study to assess the efficacy and safety of bendamustine plus rituximab in patients affected by chronic lymphocytic leukemia Type of study: prospective, observational study. Population: This cohort study will recruit chronic lymphocytic leukemia (CLL) patients who were treated with first and second-line Bendamustine plus Rituximab (BR) from January 2008 to December 2014 from European centres adhering to - the ERIC group - the GIMEMA group

6 Inclusion criteria - Diagnosis of CLL / Small Lymphocytic Lymphoma (CLL/SLL) according to the World Health Organisation (WHO) classification Previously untreated CLL requiring therapy according to the NCI criteria and treated with at least one cycle of BR as first-line treatment. - CLL that received one previous line of treatment using alkylating agents and/or purine analogues with or without monoclonal antibodies, requiring second-line therapy according to the NCI criteria and treated with at least one cycle of BR. - Age 18 years. - Signed written informed consent according to ICH/EU/GCP and national local law.

7 Exclusion criteria - Patients who have received 2 or more lines of prior therapy - Patients with: Transformation of CLL to aggressive lymphomas (Richter s Syndrome). HIV infection. Active and uncontrolled HCV and/or HBV infections or liver cirrhosis.

8 Objectives The primary objective of the study is to observe the progression-free survival in CLL patients treated with first and second-line BR regimen. The secondary objectives are to assess in CLL patients treated by the BR regimen in first line and as second line treatment: - Time to next treatment (TTNT). - Complete response (CR) rate. - Overall response rate (ORR). - Overall survival (OS). - Safety of the combination BR.

9 Efficacy and tolerability of Bendamustine and Rituximab in first line and second line treatment in CLL An observational study proposed by the ERIC-GIMEMA groups Methods «Homogeneous» collection of data based on review of clinical records - Caveats ^ selection bias ^ assessment of progression ^ recording of AE Expected results on «real-world patients» Efficacy Doses planned / administered Tolerability in patients with coexisting medical conditions AIHA

10 Potential number of patients and referent investigators* Czech R Sweden Croatia Spain France Denmark Greece Turkiye Ukraine Poland Armenia Russia Italy Germany Patients Proposed Referent Investigator Martin Spacek Lotta Hansson <lotta.ha nsson@k arolinska.se> L.Forne Javier De cker La Serna Krysztof Giannop oulos Robak Antonio Cuneo Kreutzer karlanton.kreu zer@unikoeln.de * Contact with GIMEMA data centre for special regulations before submission of the dossier to national E.C.s Contact with single national centres to ensure homogeneity and accuracy of data collection

11 N. Of centres Activated centres in Italy as of May 31 st open to recruitment with EC approval (waiting for administrative approval) wating for EC approval open to recruitment with EC approval (waiting for administrative approval) wating for EC approval GIMEMA ERIC LLC1315 BR study

12 Activated centres in Spain as of May 31st 2016 Site PI EC opinion 600 Madrid - Hematology Hospital Universitario 12 De Octubre Javier De La Serna Favourable Regulatory status Open to enrollment 601 Barcellona Hematology Hospital Clinic Julio Delgado Favourable Open to enrollment 602 Marbella (Malaga) Hospital Costa del Sol Angeles Medina Perez Favourable Open to enrollment 603 Salamanca Marcos González Under consideration 604 Hospital Santa Creu I Sant Pau, Barcelona Carol Moreno Under consideration

13 Number of patients enrolled by centre CENTER Ferrara Azienda Ospedaliero Universitaria Dipartimento di Scienze Mediche Sezione di Ematologia e Fisiopatologia dell'emostasi ENROLLED PATIENTS 14 Madrid - Hematology Hospital Universitario 12 De Octubre 12 Verona Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. 8 Milano Unità Trapianto di Midollo Ist. Nazionale Tumori 8 Latina UOC di Ematologia con trapianto Ospedale S. Maria Goretti 6 Catanzaro Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia 5 Ascoli U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno 5 Piacenza Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale G. da Saliceto TOTAL 59 1 As of 31 May 2016

14 N. of cases enrolled (February-May 2016) February March April May Total As of 31 May 2016

15 Timeline November 2015: submission of the protocol to the E.C. of the coordinating centre Institute of Hematology, University of Ferrara January 2016: Submission of the protocol to GIMEMA and ERIC centres February 2016: ecrf database open May-July 2016: speeding up the procedures contact with reference investigators in each country contact with each single centre in Italy December 2016 database lock

16 Bendamustine + Rituximab (BR) Project For any question please contact Antonio Cuneo Carol Moreno Data centre: Enrico Crea cut@unife.it cmorenoa@santpau.cat e.crea@gimema.it